Evidence map›Paper›PMID 42784584›Full record

ArticlePloS one2026

Resmetirom attenuates atherosclerosis-associated dyslipidemia and vascular inflammation in high-fat diet-fed ApoE-/- mice.

Xuedong Bai, Wenjie Fei, Jingzhou Fang, Chaomin Kong, Yaqi Xiang, Yuele Tian, Limin Wei

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Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Xuedong BaiDepartment of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, China.ORCID https://orcid.org/0009-0008-6268-7262
Wenjie FeiDepartment of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, China.
Jingzhou FangDepartment of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, China.
Chaomin KongDepartment of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, Hebei, China.
Yaqi XiangDepartment of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, China.
Yuele TianDepartment of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, China.
Limin WeiDepartment of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAtherosclerosis is driven by interacting lipid and inflammatory pathways. There remains a pressing clinical need for drugs that exert both lipid-lowering and vascular anti-inflammatory effects. Studies have suggested that thyroid hormone receptor β (THR-β) agonists can alleviate atherosclerosis while avoiding the cardiotoxic adverse effects associated with thyroid hormone. Resmetirom is an oral, once-daily, liver-targeted selective THR-β agonist. It has attracted attention for improving lipid metabolism, yet its effects on vascular inflammatory phenotypes remain poorly clarified. We investigated the effects of resmetirom on atherosclerosis-associated dyslipidemia, plaque burden and vascular inflammatory phenotypes.

methodsApolipoprotein E-deficient (ApoE-/-) mice fed a high-fat diet (HFD) for 8 weeks were randomized to vehicle, low-dose (3 mg/kg/day), or high-dose (10 mg/kg/day) resmetirom for eight weeks (n = 10 per group). Serum lipids, inflammatory cytokines, aortic plaque morphology, NLRP3 inflammasome signaling, NF-κB activation, oxidative stress, and macrophage polarization were analyzed by one-way ANOVA with Tukey post hoc testing; dose-response regression was performed across disease-bearing groups.

resultsResmetirom treatment reduced aortic plaque burden, corrected atherogenic dyslipidemia, and suppressed aortic NLRP3 and caspase-1 expression in a dose-dependent manner. High-dose resmetirom lowered low-density lipoprotein cholesterol (LDL-C) by 39.48%, and reduced aortic lipid accumulation on Oil Red O staining compared to model controls. Additionally, it suppressed interleukin-1β (IL-1β) by 59.28%; Western blotting showed lower p-p65/total p65 ratio and higher IκBα/GAPDH abundance. Flow-cytometric ROS intensity decreased by 35.56%, and the M1/M2 macrophage ratio decreased by 72.81%. Exploratory cross-assay analyses showed coherent associations among systemic cytokines and aortic NF-κB/ROS/macrophage readouts.

conclusionsResmetirom attenuated atherosclerosis-associated dyslipidemia, plaque burden and vascular inflammation in HFD ApoE-/- mice. The data support an association between resmetirom treatment and suppression of the NF-κB/ROS-NLRP3 inflammatory phenotype, warranting mechanistic validation in models with direct pathway perturbation. These findings support its translational potential in atherosclerotic cardiovascular disease.

Indexed as

Apolipoproteins EAtherosclerosisDiet, High-FatDyslipidemiasVasculitisAnimalsCytokinesInflammationMaleMiceMice, Inbred C57BLMice, KnockoutNF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinOxidative StressApolipoproteins ECytokinesNF-kappa BNLR Family, Pyrin Domain-Containing 3 Protein

Identifiers

PMID42784584
PMCPMC13606967

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.